Relative importance of composition structures and biologically meaningful logics in bipartite Boolean models of gene regulation

Abstract

Boolean networks have been widely used to model gene networks. However, such models are coarse-grained to an extent that they abstract away molecular specificities of gene regulation. Alternatively, bipartite Boolean network models of gene regulation explicitly distinguish genes from transcription factors (TFs). In such bipartite models, multiple TFs may simultaneously contribute to gene regulation by forming heteromeric complexes, thus giving rise to composition structures. Since bipartite Boolean models are relatively recent, an empirical investigation of their biological plausibility is lacking. Here, we estimate the prevalence of composition structures arising through heteromeric complexes. Moreover, we present an additional mechanism where composition structures may arise as a result of multiple TFs binding to cis-regulatory regions and provide empirical support for this mechanism. Next, we compare the restriction in BFs imposed by composition structures and by biologically meaningful properties. We find that though composition structures can severely restrict the number of Boolean functions (BFs) driving a gene, the two types of minimally complex BFs, namely nested canalyzing functions (NCFs) and read-once functions (RoFs), are comparatively more restrictive. Finally, we find that composition structures are highly enriched in real networks, but this enrichment most likely comes from NCFs and RoFs.

Lhx3/4 initiates a cardiopharyngeal-specific transcriptional program in response to widespread FGF signaling

“…Current models of signal-dependent transcription do not indicate whether lineage-determining factors instruct or facilitate lineage-specific responses to pleiotropic signals [ 22 , 23 , 103 , 104 ]. The precise contribution of lineage-determining factors may be determined by their interactions with additional cofactors.…”